Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Oncol. 2022 May 1;34(3):234-242. doi: 10.1097/CCO.0000000000000831.
The genomic and immunologic profiling of renal cell carcinoma (RCC) has provided the impetus for advancements in systemic treatments using combination therapy - either with immune check point inhibitor (ICI) + ICI or with ICI + targeted therapy. This approach has been examined in several landmark trials, treating both clear cell (ccRCC) and nonclear cell (nccRCC) histologies. In this review, we highlight systemic therapy advancements made in this new decade, the 2020s.
Targeting the programmed death receptor 1/PD-L1 pathway has created more tolerable and effective immunotherapy regimens, expanding the applications of ICIs. These new applications, paired with trial data, include ICI monotherapy in nccRCC and adjuvant pembrolizumab in resected, high-risk RCC. In addition, ICI + ICI and ICI + TKI combination therapy have demonstrated oncologic efficacy in advanced ccRCC and sarcomatoid RCC. Similar progress has been noted regarding new targeted therapies. Along the hypoxia inducible factor pathway, belzutifan has received FDA approval in von Hippel-Lindau-associated RCC. In addition, in papillary RCC, agents such as cabozantinib target the MET proto-oncogene pathway and have demonstrated impressive oncologic outcomes.
The 2020s utilize the molecular profiling of advanced RCC as a scaffold for recent trials in immunotherapy and targeted therapies. Going forward, emphasizing patient-reported outcomes and careful clinical trial construction remain critical to improve systemic therapy in RCC.
肾细胞癌（RCC）的基因组和免疫组学分析为联合治疗（免疫检查点抑制剂 [ICI] + ICI 或 ICI + 靶向治疗）的系统治疗进展提供了动力。这一方法已在几项具有里程碑意义的试验中进行了检验，适用于透明细胞（ccRCC）和非透明细胞（nccRCC）组织学。在这篇综述中，我们强调了新十年（21 世纪 20 年代）在系统治疗方面取得的进展。
靶向程序性死亡受体 1/PD-L1 通路已创造出更耐受和有效的免疫治疗方案，扩大了 ICI 的应用。这些新的应用与试验数据相结合，包括 nccRCC 的 ICI 单药治疗和高风险 RCC 切除术后的辅助 pembrolizumab 治疗。此外，ICI + ICI 和 ICI + TKI 联合治疗在晚期 ccRCC 和肉瘤样 RCC 中显示出抗肿瘤疗效。在新的靶向治疗方面也取得了类似的进展。在缺氧诱导因子通路中，belzutifan 已获得 FDA 批准用于 von Hippel-Lindau 相关性 RCC。此外，在乳头状 RCC 中，卡博替尼等药物靶向 MET 原癌基因通路，取得了令人印象深刻的肿瘤学结果。
21 世纪 20 年代利用晚期 RCC 的分子谱作为免疫治疗和靶向治疗近期试验的支架。展望未来，强调患者报告的结果和仔细的临床试验构建仍然是改善 RCC 系统治疗的关键。
